Zeinmersome nanocarriers for drug delivery to the liver

Abstract

Zeinmersomes (ZMS) comprising zein, a phospholipid and a PEG-polymer are formulated to encapsulate a drug of interest. Olmesartan medoxomil (OM) is encapsulated in the ZMS (OM-ZMS) for oral administration and taken up by the liver where OM diffuses from the ZMS nanocarrier. OM concentrations in liver were at least 8 times higher than that measured in plasma. Established fibrosis was reversed in a thioacetamide-induced rat model of human chronic hepatic fibrosis. The OM-ZMS provides a hepatic drug delivery system that reduces the potential of side-effects caused by OM, including OM-associated sprue-like enteropathy, to treat chronic hepatic fibrosis and associated duodenal changes.

We claim: 
     
       1. A pharmaceutical composition of a drug encapsulated in a zeinmersome, comprising a mixture of zein, an amphiphilic copolymer and at least one phospholipid,
 wherein the zein, the amphiphilic copolymer and the at least one phospholipid form a lipid bilayer, and 
 wherein the lipid bilayer encapsulates a suitable amount of the drug within a nanosized zeinmersome vesicle bounded by the lipid bilayer, 
 wherein the size range of the zeinmersome is 95 to 200 nm in diameter. 
 
     
     
       2. The pharmaceutical compostition of  claim 1 , wherein the amphiphilic copolymer is poly (ethylene glycol) methyl ether-block-poly (lactide-co-glycolide) (PEG-PLGA). 
     
     
       3. The pharmaceutical composition of  claim 1 , wherein the at least one phospholipid is selected from the group consisting of phosphatidylcholine, phosphatidic acid, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol phosphate, phosphatidylinositol bisphosphate and phosphatidylinositol trisphosphate. 
     
     
       4. The pharmaceutical composition of  claim 1 , wherein the drug is olmesartan, olmesartan medoxomil or (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 5-(2-hydroxypropan-2-yl)-2-propyl-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylate. 
     
     
       5. The pharmaceutical composition of  claim 4 , wherein the drug present in the zainersome is at a concentration in the range of 3% to 15% w/w.